Research: The broad spectrum of VIP biological functions are mediated by its receptor. In the lung, VIP acts as a potent smooth muscle relaxant and it may also regulate lung cancer proliferation. The long-term goal of this proposal is to determine molecular mechanisms that regulate VIP receptor expression during development and in disease. The specific aims are to isolate and characterized the rat VIP receptor gene (2). Identity regulatory elements and factors that control VIP receptor transcription in both normal and cancerous lung cells transfection and DNA-protein binding assays (3). Study the regulation of VIP receptor expression during development by in situ hybridization and by homologous recombination to generate mice that lack functional VIP receptors. These studies will provide important insight into the physiology of VIP receptor regulation and function to this ubiquitous hormone. This will lead to enhanced understanding mechanisms for VIP-responsive malignancies. Candidate: Dr. Lin Pei, M.D., Ph.D., has a strong background training in molecular biology. During early postdoctoral training at UCLA, she also acquired skills in protein chemistry. This will enable her to effectively perform and interpret the experiments in this proposal. Dr. Pei is committed to applying molecular biological techniques to answer questions of disease pathophysiology and is embarked on a career in academic medicine. She is assured of Departmental support as an independent faculty member both during and by the end of the award. Environment: The applicant will perform the research in the well-equipped laboratory of the sponsor which is funded as a NIDDK Program Project in endocrine aspects of neoplasia. As such, Dr. Pei's proposal will meet with the overall goals of the group. She will have full access to all core facilities available in the Davis Research Building including molecular oligonucleotide synthesis, transgenic mouse and vivarium. There are weekly research-in-progress laboratory meeting, departmental research seminars and visiting scientists (growth factors, transcription, gene regulator) providing continued exposure to basic and clinical research advances. In addition, Dr. Pei will enjoy the continued exposure to the expert endocrine faculty at Cedars-Sinai, as well as associated productive groups in molecular genetics, membrane biology, transplantation biology, virology and protein chemistry.